In most cases, surgery can successfully remove basal cell carcinoma (BCC) from the eyelid. However, surgery or radiotherapy is not an option for some patients because of the high risk of severe ocular morbidity should the disease spread or recur. Vismodegib, an inhibitor of the hedgehog signaling pathway, is emerging as the primary therapy for this subtype. The purpose of this review was to establish the place of surgery following treatment with vismodegib. To identify studies that analyzed the efficacy of vismodegib in the treatment of basal cell carcinoma of the eyelid, a search of the literature was conducted for articles published up to March 2021 in PubMed, the Cochrane Library, ScienceDirect, and Embase. Vismodegib as neoadjuvant therapy in locally advanced eyelid BCC when surgery and/or radiotherapy are contraindicated was supported by level 1 evidence, and was well tolerated. After mapping or during residual tumor resection, if frozen sections or Mohs surgery are performed, level 3 evidence was found for the role of surgical excision of clinically suspicious lesions and the indication of eyelid reconstruction. For advanced periorbital BCC, vismodegib is a safe and effective treatment option. Vismodegib, an inhibitor of the hedgehog signaling pathway, may be used to treat patients with these difficult tumors.